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Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) using a T-cell replete HLA-haploidentical graft (haplo-HSCT) has become routine practice in many centers worldwide for patients lacking a matched sibling or unrelated donor [1]. This procedure has been reconsidered fifteen years ago after demonstration by the Baltimore group that the use of post-transplant cyclophosphamide (PTCy) as graft-versus-host disease (GVHD) prophylaxis allowed for a drastic decrease of the incidence of severe and fatal acute (a) or chronic (c) GVHD [2]. Mechanisms underlying the efficacy of PTCy include the induction of dysfunctional alloreactive T cells, T-cell suppression and, more importantly, promotion of the rapid and preferential recovery of CD4 + CD25+Foxp3+ regulatory T cells (Treg) [3].
Since the princeps publication in 2008 [2], several comparative retrospective studies have shown that haplo-HSCT could achieve similar outcomes compared to matched donor HSCT [4,5,6,7]. PTCy is thus nowadays more and more applied to the matched setting as GVHD prophylaxis and yields a reduced incidence of GVHD [8]. The Société Francophone de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC), has also conducted the only prospective study showing the equivalence of haplo-HSCT and matched unrelated allotransplant procedures [9].
It appears however that survivals are disappointing for patients with myeloid malignancies receiving Allo-HSCT, due to a high incidence of relapse when considering the non-myeloablative (NMA) conditioning regimen used by the Baltimore team and combining fludarabine, low doses of cyclophosphamide and total body irradiation (TBI). Indeed, the 3-year overall survival (OS) was 45% for patients transplanted for a myelodysplastic syndrome (MDS) or myeloproliferative neoplasm (MPN), and only 35% for patients transplanted for acute myeloid leukemia (AML) [10].
New platforms have however been established to improve these results and two strategies can be considered, either by replacing a conditioning regimen drug by another with more anti-leukemic activity (for example clofarabine instead of fludarabine) or less toxicity (for example treosulfan instead of busulfan), or intensifying the conditioning regimen (for example use of myeloblative conditioning, adding thiotepa or melphalan) [11]. In France, two platforms are particularly considered for haplo-HSCT. The Clo-Baltimore (CloB) regimen is based on the cyclophosphamide, fludarabine and TBI Baltimore backbone [2], but fludarabine is replaced by the second-generation nucleoside analogue clofarabine, and peripheral blood stem cell (PBSC) is used instead of bone marrow as the graft source [12]. The second one combines reduced doses of thiotepa and busulfan with fludarabine (TBF-RIC) [13]. Both regimens are classified as intermediate intensity according to the Transplant Conditioning Intensity (TCI) score [14]. Both have shown interesting outcomes for the treatment of myeloid malignancies with two-year progression-free survival (PFS) around 56/58%, two-year OS between 60/67% and low rates of acute and chronic GVHD, especially with the addition of antithymocyte globulin (ATG) as part of the conditioning [15, 16]. This suggests better efficiency compared to the original Baltimore backbone. Moreover, if no comparison of CloB vs Baltimore regimens exists, a retrospective study has compared TBF RIC vs Baltimore NMA regimens demonstrating the superiority of the former only in younger patients ( < 60 yo) providing better OS and PFS due to a higher incidence of relapse with the latter. In older patients, survivals were similar but the Baltimore NMA regimen was associated with lower non relapse mortality (NRM) [17].
Yet, no comparison of the two regimens (CloB vs TBF) has been performed. Here, a propensity score matching was used in order to evaluate the superiority of one regimen over the other in the treatment of patients with myeloid malignancies receiving a haplo-HSCT.